Development of Defensive Behavior and Social Stress Consequences

防御行为的发展和社会压力后果

基本信息

批准号：
8508313
负责人：
SEEMA BHATNAGAR
金额：
$ 40.2万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8508313
关键词：
Acute Address Adolescence Adolescent Adolescent Development Adult Aggressive behavior Anxiety Arousal Basic Science Behavior Behavioral Brain Cognition Cognitive Complement Coping Behavior Data Development Disease Etiology Female Fright Future Growth Human Life Light Mediating Mediator of activation protein Mental Depression Mental Health Mental disorders Modeling Mood Disorders Neural Pathways Neuroanatomy Neurobiology Neurons Norepinephrine Odors Peptides Phenotype Physiological Play Rattus Research Rodent Role Sex Characteristics Shapes Social Behavior Social Interaction Staging Stimulus Stress Stress and Coping System Testing Time adverse outcome affiliative behavior age related base biological adaptation to stress cognitive function coping early adolescence locus ceruleus structure male neural circuit neurobehavioral neurobiological mechanism neurodevelopment norepinephrine system physical conditioning programs relating to nervous system response sex social social stress

项目摘要

DESCRIPTION (provided by applicant): Social stress has adverse consequences for physical and mental health throughout life and its impact may be particularly relevant during adolescence as this is a time of substantial growth and reorganization of brain circuits. To date, most basic research into the behavioral and physiological consequences of social stress has focused on adult male rodents. The proposed research uses a model of rat social stress, "the resident- intruder model", to characterize the neurobehavioral responses to, and consequences of, social stress at different stages of adolescent development compared to adulthood. This research also takes on the important challenge of investigating sex differences in the response to social stress or its consequences. The research program proposed here is based on preliminary data indicating that the defensive subordinate response to an aggressive conspecific develops throughout adolescence into adulthood. Temporally correlated to this is a shift away from active coping strategies in response to subsequent challenges. These age-related behavioral differences are associated with distinct changes in locus coeruleus (LC) neuronal activity. Therefore, this proposal tests the central hypothesis that social stress in early adolescence disrupts the ontogeny of specific neural pathways important for regulating the development of subordinate defensive behaviors and that this disruption has effects on behavior and cognition in adolescence that endure into adulthood. This hypothesis will be tested in three specific Aims. Aim 1 will identify and compare neural circuits engaged by social stress at different stages of adolescence and in adulthood using a functional neuroanatomy approach and examining changes in peptide systems related to social behavior and stress. Aim 2 will characterize and compare responses of LC neurons to the social stress at different stages of adolescence and in adulthood. Aim 3 will examine specific behavioral and cognitive consequences of social stress during adolescence and evaluate the endurance of these effects. Because some of the neural substrates being investigated in Aims 1 and 2 have been implicated in the behavioral endpoints being tested in AIM 3, the studies are organized to reveal how the neural substrates and circuits involved in the initial response to social stress (the defensive behaviors) at a particularly time in development play a role in determining the subsequent acute and long-term consequences of social stress. Together, the proposed studies will provide critical information about developmental and sex differences in defensive behaviors and in the consequences of social stress. Given the impact of social stress on mental health these studies will advance our understanding of the development of psychiatric disorders in humans and on the neurobiological basis for gender differences in the onset and etiology of these diseases.)

描述（由申请人提供）：社会压力会对一生的身心健康产生不利影响，其影响在青春期尤其重要，因为这是大脑回路大幅生长和重组的时期。迄今为止，关于社会压力的行为和生理后果的大多数基础研究都集中在成年雄性啮齿动物上。拟议的研究使用大鼠社会压力模型，即“居民-入侵者模型”，来描述青少年与成年相比不同发展阶段对社会压力的神经行为反应及其后果。这项研究还面临着调查社会压力或其后果反应中的性别差异的重要挑战。这里提出的研究计划基于初步数据，表明对攻击性同类的防御性下属反应会在青春期到成年期间发展。与此时间相关的是应对后续挑战的积极应对策略的转变。这些与年龄相关的行为差异与蓝斑（LC）神经元活动的明显变化有关。因此，该提议检验了一个中心假设，即青春期早期的社会压力会扰乱特定神经通路的个体发育，这些神经通路对于调节从属防御行为的发展很重要，并且这种扰乱会对青春期的行为和认知产生影响，并持续到成年。这一假设将在三个具体目标中得到检验。目标 1 将使用功能性神经解剖学方法来识别和比较青春期和成年不同阶段受社会压力影响的神经回路，并检查与社会行为和压力相关的肽系统的变化。目标 2 将描述并比较青春期和成年不同阶段 LC 神经元对社会压力的反应。目标 3 将研究青春期社会压力的具体行为和认知后果，并评估这些影响的持久性。由于目标 1 和 2 中研究的一些神经基质与 AIM 3 中测试的行为终点有关，因此组织这些研究是为了揭示神经基质和回路如何参与对社会压力的初始反应（防御行为））在发展的特定时期，在决定社会压力随后的严重和长期后果方面发挥着作用。总之，拟议的研究将提供有关防御行为和社会压力后果的发育和性别差异的关键信息。鉴于社会压力对心理健康的影响，这些研究将增进我们对人类精神疾病的发展以及这些疾病的发病和病因学中性别差异的神经生物学基础的理解。）